© 2020 Elsevier B.V.Atorvastatin is a statin group HMG-CoA reductase inhibitor drug that is commonly used to adverse cardiovascular events and to lower blood total cholesterol and LDL-cholesterol. In recent years, atorvastatin has been reported to exert anti-inflammatory activity and also inhibit degeneration of periodontal collagen fibers in periodontal diseases. However, the solubility of atorvastatin in water is very low (0.1 mg mL−1), which results in reduced bioavailability. In order to enhance its solubility, we have prepared solid dispersions (SDs) of atorvastatin at different drug: polymer ratios (1:9 and 1:12), using different polymers (polyethylene glycol 6000 (PEG 6000), Pluronic F-68 (PL F-68), chitosan and preparation methods (co-evaporation, melting, co-grinding and kneading). The characterization of the SDs was performed using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and X-ray powder diffraction (XRD). Further, the atorvastatin SDs were incorporated into chitosan gel at 2% concentration, intended for local application in treatment of periodontal disease. The viscosity and bioadhesive property of the gels were measured, and in vitro drug release studies were performed. Additionally, the anti-inflammatory activity of the formulations was performed using tumor necrosis factor (TNF)-alfa induced human gingival fibroblast (hGF) cells. Proinflammatory cytokine (IL-1β, IL-6, IL-8) and anti-inflammatory cytokine (IL-10, TGF-β1, TGF-β2, TGF-β3) levels were measured following application of the formulations. A significant increase in solubility was achieved with the SDs. The highest solubility was obtained with Pluronic F-68 using co-evaporation method at 1:12 ratio (5,55 mg/mL). Chitosan gels incorporated with SDs of atorvastatin exhibited suitable viscosity and bioadhesive property for high retention time of the drug at the application site. The drug release from the gels incorporated with SDs of atorvastatin was found to be higher than that of crystalline atorvastatin in chitosan gels. Decrease in cytokine levels was observed to be enhanced with the with SDs incorporated into chitosan gel, indicating higher anti-inflammatory activity. The preparation method used for SDs was found to have no significant effect on cytokine levels.